Synovial fluid profile dictates nanoparticle uptake into cartilage - implications of the protein corona for novel arthritis treatments
Journal article, 2022
Objective: Drug delivery strategies for joint diseases need to overcome the negatively charged cartilage matrix. Previous studies have extensively investigated particle approaches to increase uptake efficiency by harnessing the anionic charge of the cartilage but have neglected to address potential interactions with the protein-rich biological environment of the joint space. We aimed to evaluate the effects of hard protein coronas derived from osteoarthritis (OA) and rheumatoid arthritis (RA) patient synovial fluids as well as the commonly used fetal calf serum (FCS) on nanoparticle (NP) uptake into tissues and cells.
Methods: We developed a NP panel with varying PEGylation and incubated them with synovial fluid from either OA, RA patients or FCS. We evaluated the effects of the formed NP-biocorona complex uptake into the porcine articular cartilage explants, chondrocytes and monocyte cell lines and primary patient FLS cells. Proteins composing hard biocoronas were identified using a quantitative proteomics approach.
Results: Formed biocoronas majorly impacted NP uptake into cartilage tissue and dictated their uptake in chondrocytes and monocytes. The most suitable NP for potential OA applications was identified. A variety of proteins that were found on all NPs, irrespective of surface modifications. NP-, and protein-specific differences were also observed between the groups, and candidate proteins were identified that could account for the observed differences.
Conclusions: This study demonstrates the impact of protein coronas from OA and RA patient synovial fluids on NP uptake into cartilage, emphasizing the importance of biological microenvironment considerations for successful translation of drug delivery vehicles into clinics.
Synovial fluid
Protein corona
Drug delivery
Arthritis
Cartilage
Author
Ula von Mentzer
Chalmers, Biology and Biological Engineering, Chemical Biology
Tilia Selldén
Chalmers, Biology and Biological Engineering, Chemical Biology
Loise Råberg
Chalmers, Biology and Biological Engineering, Chemical Biology
Gizem Erensoy
Chalmers, Biology and Biological Engineering, Chemical Biology
A. K. Hultgård Ekwall
University of Gothenburg
Sahlgrenska University Hospital
Alexandra Stubelius
Chalmers, Biology and Biological Engineering, Chemical Biology
Osteoarthritis and Cartilage
1063-4584 (ISSN) 1522-9653 (eISSN)
Vol. 30 10 1356-1364Gender Initiative for Excellence (Genie)
The Chalmers University Foundation, 2019-01-01 -- 2028-12-31.
Precision Medicine for Rheumatoid Arhtritis: Utilizing Disease Mechanisms to Achieve Self-Adjusting Nanotherapeutics
Stiftelsen Anna-Greta och Holger Crafoords fond (CR2021-0024), 2021-10-01 -- 2023-08-15.
Areas of Advance
Nanoscience and Nanotechnology
Health Engineering
Subject Categories (SSIF 2011)
Medicinal Chemistry
Infrastructure
Chalmers Materials Analysis Laboratory
DOI
10.1016/j.joca.2022.07.002
PubMed
35840018